DETAILED ACTION
The examiner of record has changed. Please direct all further correspondence to ZACHARY J MIKNIS whose telephone number is (571) 272-7008.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
The amendment and remarks of 20 March 2026 are entered.
Claims 1-3 have been canceled. Claims 4-17 are pending and are being examined on the merits.
The objection to claim 10 is withdrawn in light of the amendment filed 20 March 2026.
The rejection of claims 5 and 10 under 35 U.S.C. 112(b) is withdrawn in light of the amendment filed 20 March 2026.
The rejection of claim 5 under 35 U.S.C. 112(d) is withdrawn in light of the amendment filed 20 March 2026.
The rejection of claims 1-4 and 7-9 under 35 U.S.C. 102(a)(1) as being anticipated by Kaur et al. (668) is withdrawn in light of the amendment filed 20 March 2026.
The rejection of claims 1-3 under 35 U.S.C. 103 as being unpatentable over Kaur et al. (668) is withdrawn in light of the cancellation of said claims in the amendment filed 20 March 2026. The rejection of claims 4-11 is maintained, with the Examiner’s response found below.
The rejections for nonstatutory double patenting are withdrawn in light of the amendment filed 20 March 2026.
New grounds of rejection are presented below in response to Applicants’ amendment.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). See claims 4 and 7 reciting the sequence VPWXEPAYQRFL.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 4 and 7 contain the trademark/trade name VivoTag. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a protein tag and, accordingly, the identification/description is indefinite. The dependent claims do not remedy this deficiency.
Claims 4 and 7 claim “VPWxEPAYWrFL ((SEQ ID NO: 55) a D-amino acid substituted analogue of VPWXEPAYQRFL)”. This is indefinite because the disclosed sequence in SEQ ID NO: 55 is FITC-Aβ-VPWXEPAYQRFL. Since there is a discrepancy between what is claimed and what is disclosed in the CRF, it is not clear if the claim is directed to a derivative having the FITC-Aβ N-terminus or to the sequence as claimed lacking this element. The dependent claims do not remedy this deficiency.
Claims 4 and 7 claim “FITC-Aβ-VPWXEPAYQRFL ((SEQ ID NO: 56) a D-amino acid substituted analogue of VPWxEPAYQrFL)”. This is indefinite because the disclosed sequence in SEQ ID NO: 55 is VivoTag-Aβ-VPWxEPAYQrFL. Since there is a discrepancy between what is claimed and what is disclosed in the CRF, it is not clear if the claim is directed to a derivative having the VivoTag-Aβ N-terminus or to the sequence as claimed lacking this element. The dependent claims do not remedy this deficiency.
Claims 4 and 7 claim “VivoTag-Aβ-VPWXEPAYQRFL ((SEQ ID NO: 57) a fluorescently labeled derivative of VPWxEPAYQrFL)”. This is indefinite because SEQ ID NO: 57 is not present in the CRF. Since there is a discrepancy between what is claimed and what is disclosed in the CRF, it is not clear what sequence the claims are directed towards. The dependent claims do not remedy this deficiency.
Claims 13, 14, 16, and 17 claim “VPWxEPAYQrFL (SEQ ID NO: 55)”. The claim is indefinite because it is inconsistent with SEQ ID NO: 55 as disclosed, which contains the sequence FITC-Aβ-VPWXEPAYQRFL. The sequence as found in the claim lacks the N-terminal FITC-Aβ. Amino acids in lower-case letters are generally interpreted as D-amino acids, which is also not found within SEQ ID NO: 55. Given these discrepancies between the claimed and disclosed sequence, one of ordinary skill in the art cannot determine the metes and bounds of the claims.
For the purposes of prior art, each sequence is interpreted as being directed to the sequence claimed as opposed to that found in the CRF.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 4-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tong et al. (Pharmaceutics 14:1036, published 11 May 2022, hereafter referred to as Tong).
Tong discloses the peptide KK-11, including its D-amino acid substituted analog VPWxEPAYQrFL (see e.g. Abstract). This along with anticancer drugs doxorubicin or MAC-3-190 were co-administered (see e.g p.2, last paragraph). Tong also discloses KK-11 peptides including FITC-Aβ-VPWXEPAYQRFL and VivoTag-Aβ-VPWxEPAYQrFL (see e.g. Table 2). This anticipates claim 4.
With respect to claim 5, doxorubicin and MAC-3-190 read upon the claimed chemotherapeutic agents as anthracyclines and neuronal nitric oxide synthase inhibitors, respectively.
With respect to claim 6, as noted above one combination is between d-KK-11 and doxorubicin.
With respect to claim 7, the combination of Tong is utilized in a melanoma xenograft model in mice, i.e. it anticipates treating cancer.
With respect to claims 8 and 9, as noted above Tong discusses a melanoma xenograft model for treatment.
With respect to claim 10, as noted above doxorubicin and MAC-3-190 read upon the claimed chemotherapeutic agents.
With respect to claim 11, as noted above one disclosed combination is with doxorubicin.
With respect to claim 12, as noted above one disclosed combination is with MAC-3-190.
With respect to claims 13 and 14, as noted above the combination is VPWxEPAYQrFL with either doxorubicin or MAC-3-190 as disclosed by Tong.
With respect to claim 5, as noted above Tong discloses combinations with MAC-3-190.
With respect to claims 16 and 17, as noted above the combination is VPWxEPAYQrFL with doxorubicin or MAC-3-190.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 4-11, 13, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Kaur et al. (WO 2011/103668 Al, 2011; 63 pages, hereafter referred to as Kaur et al. (668)).
Kaur et al. (668) discloses the use of chemotherapeutic agents in combination with the tumor-targeting peptides disclosed in their application (see page 30 lines 24-26). Kaur et al. (668) discloses that the peptides are effective carriers or delivery agents for cytotoxic payloads such as chemotherapy or radionuclides because of their ability to target particular cell surfaces (see page 30 lines 24-26). They also disclose that the peptides can be conjugated to micelles for targeted delivery of anticancer drug to cancer cells in vitro (see page 10 line 32 and page 11 line 1). The peptides capable of binding tumors that they disclose include VPWXEPAYQRFL (see Table 1). Kaur et al. (668) discloses that D-amino acids may be incorporated into peptides to increase enzymatic stability (see p.24 lines 24-26).
The difference between Kaur and the claimed invention is that Kaur does not explicitly disclose preparation of VPWxEPAYQrFL in combination with an anticancer agent.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the disclosure of Kaur et al. (668) concerning the tumor-binding peptides including VPWXEPAYQRFL by introducing D-amino acids as suggested in a systematic manner and in that way arrive at VPWxEPAYQrFL in combination with cytotoxic payloads. The rationale comes from the disclosure of Kaur et al. (668) directing one to utilize D-amino acids for enzymatic stability. There would have been a reasonable expectation of success because Kaur et al. (668) offers guidance on introduction of D-amino acids, which was also a known technique to promote enzymatic stability for short peptides. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claim 5, although Kaur et al. (668) disclose a pharmaceutical composition comprising one of the recited tumor-binding peptides and a chemotherapeutic agent, they do not explicitly teach that the chemotherapeutic agent can be alkylating agents, anthracyclines like doxorubicin, taxanes, epithilones, histone deacetylase inhibitors, topoisomerase inhibitors, nucleoside analogs, peptide antibiotics, platinum-based agents, retinoids, vinca alkaloids, or neuronal nitric oxide synthase inhibitors.
Kaur et al. (668) does, however, disclose that it is known that doxorubicin, one of the agents listed above, can be used in combination with RGD for drug delivery. More specifically, they disclose that micelles having been surface coated with RGD peptide show an increase in the therapeutic efficacy of doxorubicin for sensitive and resistant cancers (see page 18 lines 24-26). RGD peptides, including RGDPAYQGRFL, which is disclosed in Kaur et al. (668), are tumor-targeting peptides (see page 18 lines 24-26). Kaur et al. (668) goes on to disclose that peptides like WXEAAYQRFL have similar binding efficacy and binding targets as compared to RGD peptides like RGDPAYQGRFL (see Table 1). Kaur et al. (668) further discloses that peptides like WXEAAYQRFL may be conjugated to micelles for targeted delivery of anticancer drug to cancer cells in vitro and in a mouse model, similar to the use of RGD peptides recited above (see page 18 lines 23-24).
Here, RGD peptides are similar tumor-targeting peptides with the same binding targets, and they are known to serve as effective carriers for doxorubicin in micelles. As such, Kaur et al. (668) provides a motivation to substitute the non-RGD peptides of their application, including VPWXEPAYQRFL in place of RGD peptides with a reasonable expectation of success of creating a pharmaceutical composition with doxorubicin capable of similarly binding to cancer cells and treating cancer. This is particularly clear in light of the fact that Kaur et al. (668) suggests that WXEAAYQRFL and RGDPAYQGRFL can be conjugated to micelles for targeted delivery of anticancer drug to cancer cells, and that RGD peptides like RGDPAYQGRFL can be used with doxorubicin when conjugated to micelles (see page 18 lines 23-24).
With respect to claim 6, the instant case is a substitution of one known element, the peptide VPWXEPAYQRFL disclosed in Kaur et al. (668), in place of another, an RGD peptide, to obtain predictable results. Kaur et al. (668) establishes that RGD peptides are effective in combination with doxorubicin, and they also establish that peptides like VPWXEPAYQRFL have similar binding targets and binding efficacy (see Table 1). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to substitute the peptides taught by Kaur et al. (668), including VPWXEPAYQRFL in the place of similar RGD tumor-targeting peptides used in doxorubicin delivery to yield a predictable result. This is particularly clear considering their similar function and efficacy in binding cancer cells and the prior motivation in Kaur et al. (668) to use the peptides in micelles for drug delivery (see page 18 lines 23-24 and Table 1).
With respect to claim 7, Kaur et al. (668) also discloses a method of treating cancer comprising administering a peptide to a subject, and the peptide can include one VPWXEPAYQRFL (see claim 2 and Table 1). They also disclose the use of chemotherapeutic agents in combination with one of the tumor-targeting peptides discussed above (see page 30 lines 24-26). Further, Kaur et al. (668) discloses that the peptides are effective carriers or delivery agents for cytotoxic payloads such as chemotherapy or radionuclides because of their ability to target particular cell surfaces (see page 30 lines 24-26). They also disclose that the peptides can be conjugated to micelles for targeted delivery of anticancer drug to cancer cells in vitro (see page 10 line 32 and page 11 line 1).
With respect to claims 8 and 9, Kaur et al. (668) disclose that the peptides discussed above can be synthesized on cell membranes using SPOT synthesis and then exposed to cell lines which are tumorous or cancer cell lines (see page 9 lines 9-21). Specifically, they teach that the peptides discussed above would be useful in targeting tumorous or cancerous cell lines in MDA-MB-435, a melanoma cell line (see Table 1 and page 9 lines 22-24).
With respect to claims 10 and 11, Kaur et al. disclose a method of treating cancer comprising administering a pharmaceutical composition comprising one of the peptides recited above in combination with a chemotherapeutic agent. As discussed above, they do not explicitly teach the use of doxorubicin with VPWXEPAYQRFL, but they provide a motivation. The case of claims 10 and 11 is the same substitution of one known element, VPWXEPAYQRFL, in place of another, the RGD peptides, to obtain predictable results. For the same reasoning applied to claims 5 and 6, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to substitute the peptides taught by Kaur et al. (668), including VPWXEPAYQRFL, WXEAAYQRFL, RGEPAYQRFL, RGEPAYQGRFL, and RGDPAYQGRFL, in the place of general RGD tumor-targeting peptides used in doxorubicin delivery to yield a predictable result, particularly considering their similar function and efficacy in binding cancer cells and the motivation in Kaur et al. (668) to use the peptides in micelles for drug delivery (see page 18 lines 23-24 and Table 1).
With respect to claims 13 and 16, as noted above Kaur et al. (668) provide a rationale to prepare VPWxEPAYQrFL and combine with doxorubicin either as a standalone composition or as a composition used in a method of treating cancer.
Response to Arguments:
The Applicants summarize the requirement for a conclusion of obviousness.
The Examiner finds no issues with the argument as presented.
The Applicants argue regarding claims 4 and 7 that Kaur fails to disclose or suggest the claimed peptides. The Applicants argue Kaur fails to disclose or suggest the three claimed sequences of VPWxEPAYQrFL, FITC-Aβ-VPWXEPAYQRFL and VivoTag-Aβ-VPWxEPAYQrFL. The Applicants argue Kaur does not disclose or suggest combination of those peptides with a chemotherapeutic agent, in particular doxorubicin or MAC-3-190. The Applicants argue Kaur does not disclose or suggest all limitations and therefore cannot render the claims obvious.
The Examiner disagrees. Kaur suggests the base VPWXEPAYQRFL peptide, and directly offers a rationale for introduction of D-amino acids. Preparation of VPWxEPAYQrFL is well within the level of ordinary skill in the art given the Kaur guidance with minimal effort. Similarly, Kaur offers a rationale for inclusion of chemotherapeutic agents, including doxorubicin, based on combinations with similar peptides disclosed therein. While Kaur may not disclose or suggest the FITC or VivoTag versions, the claims are not limited to only these peptides. Similarly, while Kaur may not disclose or suggest inclusion of MAC-3-190, the claims are not limited to just this chemotherapeutic agent.
The Applicants’ arguments have been considered but are not persuasive. The rejection is modified and maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached M-F 9-5 8 am – 6 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at (571) 270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Z.J.M/Patent Examiner, Art Unit 1658 /SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
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